School of Medicine and Health Sciences Poster Presentations

Title

Transplantation of p53-silenced Endothelial Progenitor Cells (EPCs) under renal capsule: a potential treatment for diabetic kidney disease (DKD)

Poster Number

142

Document Type

Poster

Status

Postdoc

Abstract Category

Cardiology/Cardiovascular Research

Keywords

diabetic kidney disease (DKD), stem cell transplantation, diabetes, proteinuria

Publication Date

Spring 2018

Abstract

Diabetic kidney disease (DKD) is a major vascular complication of diabetes, which leads to glomerulosclerosis and poor perfusion. Improving the renal vasculature may help to halt or reverse the kidney injury. Use of mesenchymal stromal cells (MSCs) in diabetic nephropathy showed some positive results. However, endothelial to mesenchymal transformation of endothelial-like structures in the kidney may occur in diabetic kidney disease (DKD) post mesenchymal cell delivery. Here, we investigated whether transplanting EPCs that have p53 gene, transiently silenced, (using Adenovirus) under renal capsule could improve kidney function in DKD mice. Methods: C57Bl6 mice were made diabetic by using STZ, next we confirmed proteinuria in STZ-induced type 1 diabetic C57BL/6J mice. We transplanted 0.3 million p53-silenced EPCs, transduced ex-vivo with Ad-p53-sh or Ad-Null-EPCs, bilaterally, under each kidney capsule. Another control was non-STZ normal mouse. Urine was collected at weeks 1, 2, 3 and 4 for volume and protein estimation. Renal blood flow was measured by laser Doppler, by exposing kidneys, immediately prior to sacrifice. Kidneys were harvested post sacrifice followed by qRT-PCR. Results: There was no proteinuria after week 2 in p53sh-EPC transplanted mouse. Enhanced blood flow (3.2 fold) was noted with delivery of p53sh-EPCs compared to null. Degree of improvement of proteinuria and renal blood flow in the diabetic mice were similar to the non-STZ mouse. Interestingly, markers for neovascularization, such as eNOS (4.5 fold, p=0.002) and VEGF-A (1.5 fold, p=0.03) were upregulated in kidney tissue , significantly, post transplantation of p53 silenced EPCs compare to null EPC transplanted kidney. Conclusion: Transient silencing of p53 gene in mouse EPCs help to improve proteinuria, diabetic polyuria and renal blood flow and may have a prominent therapeutic role in DKD.

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Transplantation of p53-silenced Endothelial Progenitor Cells (EPCs) under renal capsule: a potential treatment for diabetic kidney disease (DKD)

Diabetic kidney disease (DKD) is a major vascular complication of diabetes, which leads to glomerulosclerosis and poor perfusion. Improving the renal vasculature may help to halt or reverse the kidney injury. Use of mesenchymal stromal cells (MSCs) in diabetic nephropathy showed some positive results. However, endothelial to mesenchymal transformation of endothelial-like structures in the kidney may occur in diabetic kidney disease (DKD) post mesenchymal cell delivery. Here, we investigated whether transplanting EPCs that have p53 gene, transiently silenced, (using Adenovirus) under renal capsule could improve kidney function in DKD mice. Methods: C57Bl6 mice were made diabetic by using STZ, next we confirmed proteinuria in STZ-induced type 1 diabetic C57BL/6J mice. We transplanted 0.3 million p53-silenced EPCs, transduced ex-vivo with Ad-p53-sh or Ad-Null-EPCs, bilaterally, under each kidney capsule. Another control was non-STZ normal mouse. Urine was collected at weeks 1, 2, 3 and 4 for volume and protein estimation. Renal blood flow was measured by laser Doppler, by exposing kidneys, immediately prior to sacrifice. Kidneys were harvested post sacrifice followed by qRT-PCR. Results: There was no proteinuria after week 2 in p53sh-EPC transplanted mouse. Enhanced blood flow (3.2 fold) was noted with delivery of p53sh-EPCs compared to null. Degree of improvement of proteinuria and renal blood flow in the diabetic mice were similar to the non-STZ mouse. Interestingly, markers for neovascularization, such as eNOS (4.5 fold, p=0.002) and VEGF-A (1.5 fold, p=0.03) were upregulated in kidney tissue , significantly, post transplantation of p53 silenced EPCs compare to null EPC transplanted kidney. Conclusion: Transient silencing of p53 gene in mouse EPCs help to improve proteinuria, diabetic polyuria and renal blood flow and may have a prominent therapeutic role in DKD.